In spite of numerous observations suggesting the importance of histamine in brain function and pathology, the role of this biogenic amine in the CNS remains undefined. Investigations to date have not yielded convincing evidence that histamine serves a neurotransmitter role, either peripherally or centrally. Much more definitive evidence implicates this amine as a local regulator of microcirculation and homeostasis in connective tissue peripherally. The proposed investigation is concerned with the neurologic significance of such a local homeostatic role of histamine in brain tissue. A major objective of the proposed research is the application of newly developed molecular tracer methodology to a detailed kinetic precursor-product analysis of histamine metabolism in brain. An attempt will be made to define possible relationships of the latter to brain acid mucopolysaccharides and to the regulation of brain microcirculatory homeostasis.